The Department of Neurological Surgery at the University of Washington has a major commitment to the care and investigation of trauma to the central nervous system. In the present proposal, we describe a program project designed to support investigations focused on the general theme of the response of the CNS to injury. Because of the existing funded research in clinical head and spinal cord trauma, we have concentrated our efforts on basic studies in two general categories that influence traumatic head injury outcome: (1) Response and repair mechanisms in neurons and glia; and (2) secondary factors that compromise neural tissue. Seven projects comprise our efforts: 1) Neurotrophic factors in head injury; 2) Plasticity in the trigeminal system; 3) Expression and regulation of the immune response in the traumatized CNS; 4) Neuronal-glial interactions in axonal and dendritic growth; 5) Investigation of vasculature changes in head injury; 6) Secondary factors affecting cerebral vasculature in head injury; 7) Mechanisms and prevention of selective vulnerability to ischemia in hippocampal slice cultures. In addition, we propose postdoctoral research funding for four fellows, to encourage interdisciplinary research and the development of talented young investigators in the area of CNS trauma. We also propose a funding mechanism to encourage pilot studies to foster the development of creative new CNS trauma research. Strong, experienced cores in biostatistics and administration are also described and are important components in establishing collaborative interactions among all investigators.